crossing96/oncoscreening huggingface dataset:
Combretastatin A-4 inhibits cell growth and metastasis in bladder cancer cells and retards tumour growth in a murine orthotopic bladder tumour model.	BACKGROUND AND PURPOSE: Bladder cancer is a highly recurrent cancer after intravesical therapy, so new drugs are needed to treat this cancer. Hence, we investigated the anti-cancer activity of combretastatin A-4 (CA-4), an anti-tubulin agent, in human bladder cancer cells and in a murine orthotopic bladder tumour model. EXPERIMENTAL APPROACH: Cytotoxicity of CA-4 was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, propidium iodide (PI) staining assay and clonogenic survival assay. In vivo microtubule assembly assay, cell cycle analyses, Western blot and cell migration assay were used to study the mechanism of CA-4. The effect of intravesical CA-4 therapy on the development of tumours was studied in the murine orthotopic bladder tumour model. KEY RESULTS: CA-4 inhibited microtubule polymerization in vivo. Cytotoxic IC(50) values of CA-4 in human bladder cancer cells were below 4 nM. Analyses of cell-cycle distribution showed CA-4 obviously induced G(2)-M phase arrest with sub-G(1) formation. The analyses of apoptosis showed that CA-4 induced caspase-3 activation and decreased BubR1 and Bub3 in cancer cells. In addition to apoptosis, CA-4 was also found to induce the formation of multinucleated cells. CA-4 had a significantly reduced cell migration in vitro. Importantly, the in vivo study revealed that intravesical CA-4 therapy retarded the development of murine bladder tumours. CONCLUSIONS AND IMPLICATIONS: These data demonstrate that CA-4 kills bladder cancer cells by inducing apoptosis and mitotic catastrophe. It inhibited cell migration in vitro and tumour growth in vivo. Hence, CA-4 intravesical therapy could provide another strategy for treating superficial bladder cancers.	bladder
Papillary adenocarcinoma of the urachus presenting as an umbilical mass.	A 53-year-old Caucasian female presented with an erythematous, tender, fluctuant mass in the periumbilical region. A computerized tomography scan of the abdomen and pelvis suggested a large tumor extending from the umbilicus to the dome of the bladder with elements of tissue within the bladder consistent with a malignancy of either bladder or urachal origin. The patient subsequently underwent a cystoscopic biopsy which was positive for papillary adenocarcinoma arising in a villous adenoma. Metastatic workup revealed multiple hepatic and bilateral pulmonarynodules. Palliative laparotomywithlysis of adhesions, smallbowel resection, partial cystectomy, omentectomy, abdominal wall and umbilical resection were performed.	bladder
Molecular grade (FGFR3/MIB-1) and EORTC risk scores are predictive in primary non-muscle-invasive bladder cancer.	BACKGROUND: The European Organization for Research and Treatment of Cancer (EORTC) risk scores are not validated in an independent patient population. Molecular grade (mG) based on fibroblast growth factor receptor 3 (FGFR3) gene mutation status and MIB-1 expression was proposed as an alternative to pathologic grade in bladder cancer (BCa) [1]. OBJECTIVE: To validate the EORTC risk score and to determine its relation to mG in a series with long-term follow-up as well as to determine reproducibility of pathologic grade and mG. DESIGN, SETTING, AND PARTICIPANTS: In this multicenter study, we included 230 patients with primary non-muscle-invasive BCa (NMIBC). MEASUREMENTS: Four uropathologists reviewed the slides. FGFR3 mutation status was examined by two assays. MIB-1 was assessed by immunohistochemistry. The EORTC risk scores for recurrence and progression were determined. Multivariable analyses were used to find prognostic factors. RESULTS AND LIMITATIONS: Median follow-up was 8.62 yr (interquartile range: 6.6-11.8). FGFR3 mutations were significantly related to favorable disease parameters, whereas altered MIB-1 was frequently seen with pT1, high grade, and high EORTC risk scores. EORTC risk scores were significant in multivariable analyses for recurrence and progression. In multivariable analyses for progression and disease-specific survival, the mG had independent significance. The addition of mG to the multivariable model for progression increased the predictive accuracy from 74.9% to 81.7% (p<0.001; Mantel-Haenszel test). The mG (89%) was more reproducible than the pathologic grade (41-74%). CONCLUSIONS: We validated the EORTC risk scores for primary NMIBC in a clinical and biomarker setting. Next to EORTC risk score, mG proved highly reproducible and predictive. Our long-term results justify an independent prospective analysis of mG and EORTC risk scores.	bladder
[Localization diagnosis of carcinoma in situ of bladder cancer by pirarubicin: preliminary clinical experience].	OBJECTIVE: To investigate whether the location of carcinoma in situ (CIS) of bladder cancer could be macroscopically ascertained by instilling pirarubicin (THP) into urinary bladder. METHODS: 50 mg of THP was dissolved into 50 ml of 5% glucose solution. And the resulting solution was instilled into urinary bladder. After 15 min, the urinary bladder was observed by a cystoscopy. The study group consisted of 51 patients with bladder cancer (37 males, 14 females) and 14 patients with hematuria (8 males, 6 females), treated at our hospital from December 2007 to June 2008. RESULTS: The THP uptake was seen in 67 flat (non-tumorous) areas of bladder mucosa in 37 patients with bladder cancer. Of these, 11 lesions in 7 patients were confirmed to be CIS. The THP uptake was found in 2 flat (non-tumorous) areas of bladder mucosa in 14 patients with hematuria, 1 lesion in 1 patient was confirmed to be CIS. The sensitivity and specificity of THP uptake by CIS were 92.3% (12/13) and 86.7% (371/428) respectively. CONCLUSION: This practical method may be employed to ascertain easily the macroscopic location of CIS of bladder cancer.	bladder
[Induction of cell cycle arrest in bladder cancer RT4 cells by capsaicin].	OBJECTIVE: To study the effects of capsaicin on the growth of bladder cancer RT4 cell and its potential mechanism. METHODS: Cell counting kit-8 (CCK-8) assay and flow cytometry were employed to observe the effects of capsaicin (50, 100, 150, 200, 250 micromol/L) on cell growth, cell cycle and apoptosis. Capsaicin (0 micromol/L) was used as a control. The effects of mRNA and protein of transient receptor potential cation channel subfamily V 1 (TRPV1) on RT4 cells were tested by RT-PCR and immunofluorescence respectively. And the expressions of cell cycle protein P53, P21, CDK2 were detected by Western blot after the treatment of capsaicin. RESULTS: 100 micromol/L capsaicin significantly decreased the viability of RT4 cell [82.0% +/- 6.2% vs 100.0% +/- 12.4% (control), P = 0.036] while the cell viability was 7.8% +/- 2.9% at 250 micromol/L (P = 0.000). It was in a dose-dependent manner. On the other hand, capsaicin induced the cell cycle arrest of bladder cancer RT4 cells G(0)/G(1) phase in a dose-dependent way. The cell proportion of G(0)/G(1) phase in the control was 37.4% +/- 5.6%, however, it was 72.4% +/- 5.3% at 250 micromol/L (P = 0.000). It was showed that TRPV1 mRNA and protein were expressed in RT4 cells. After a 48-hour treatment with capsaicin, the expressions of P53 and P21 were up-regulated in contrary to the expression of CDK2. CONCLUSION: Capsaicin induces the cell cycle arrest of bladder cancer RT4 cells G(0)/G(1) phase and growth inhibition via TRPV1 receptor by modulating the expression of P53, P21 and CDK2.	bladder
Involvement of T helper type 17 and regulatory T cell activity in tumour immunology of bladder carcinoma.	T helper type 17 (Th17) and regulatory T cells (T(reg) ) play an important role in the pathogenesis of inflammation and autoimmune disorders. Recent studies have suggested that they also had an impact on tumour immunology. However, the relationship between Th17 and T(reg) cells in the pathogenesis of bladder carcinoma is still unclear. Flow cytometry was used to analyse the numbers, phenotype and cytokine production of Th17 cells in peripheral blood and tumour tissue from bladder carcinoma patients, in parallel with analysis of T(reg) cells. The suppressor capacity of T(reg) and the potential effects of interleukin (IL)-2 on the differentiation of Th17 and T(reg) cells in vitro were studied in a T cell stimulation and suppression assays. The results were as follows: Th17 cells were enriched in the tumours of patients with bladder carcinoma compared with the peripheral blood of patients and controls; patients with bladder carcinoma had a higher proportion of T(reg) cells in peripheral blood compared with healthy controls and nearly all patients examined showed a relative enrichment of tumour-infiltrating T(reg) with respect to peripheral blood; there appeared to be an inverse relationship between tumour-infiltrating Th17 and T(reg) cells; IL-2 could convert tumour-infiltrating T(reg) cells cultured in the presence of the autologous irradiated CD3(-) fraction into Th17 cells, down-regulate forkhead box P2 expression and suppressive capacity of T(reg) cells. This study is the first to define the frequency and characteristics of Th17 cells in bladder carcinoma. We suggest that the balance between Th17 and T(reg) cells may be involved in the development or progression of bladder carcinoma.	bladder
Stage pT0 at radical cystectomy confers improved survival: an international study of 4,430 patients.	PURPOSE: We describe the cancer related outcome in patients with pT0 bladder urothelial carcinoma at radical cystectomy who did not receive preoperative chemotherapy in a large multicenter series. We also compared outcomes in patients with pT0 bladder urothelial carcinoma to those in patients with other stages and assessed the effect of clinical stage on outcome. MATERIALS AND METHODS: We reviewed the records of 4,430 patients treated with radical cystectomy for bladder urothelial carcinoma without neoadjuvant chemotherapy at 12 centers in the United States, Canada and Europe. RESULTS: Of the patients 228 (5.1%) had pT0 disease at radical cystectomy. Clinical stage was cTa or cTis in 13.6% and cT1 in 29.8% of these patients, and disease was muscle invasive (cT2-4a) in 56.2%. Metastasis developed to regional lymph nodes in 17 cases (7.5%). At a median 48.2-month followup 15 patients (6.6%) had died of bladder cancer. Five-year recurrence-free and cancer specific survival estimates were 89.7% (95% CI 85.3-93.1) and 93.1% (95% CI 88.9-95.6), respectively. Disease-free and cancer specific survival in pT0 cases was similar to that in pTa/pTis cases but significantly better than in pT1 or pT2 cases. On multivariate analysis increased disease recurrence and cancer specific mortality risks were significantly associated with lymph node metastasis (each p <0.001) and female gender (p <0.001 and 0.013, respectively). CONCLUSIONS: Although stage pT0 at radical cystectomy confers a benefit in survival, some patients experience disease recurrence and eventual death. Identifying these patients may help tailor postoperative decision making in patients with pT0.	bladder
Voided urine fluorescence in situ hybridization testing for upper tract urothelial carcinoma surveillance.	PURPOSE: Fluorescence in situ hybridization is gaining popularity for transitional cell carcinoma screening. We determined the accuracy of fluorescence in situ hybridization for identifying upper tract transitional cell carcinoma. MATERIALS AND METHODS: A retrospective review of our upper tract transitional cell carcinoma database from 2005 to 2008 identified 35 patients with upper tract transitional cell carcinoma who submitted voided urine specimens for fluorescence in situ hybridization at commercial laboratory during a routine office visit. Each patient was evaluated endoscopically in the operating room within 3 months of sampling. Suspicious lesions were biopsied and treated. Transitional cell carcinoma in the lower or upper tract was proved by direct visualization, positive biopsy or upper tract cytology read as positive or highly suspicious for malignancy. RESULTS: Of the patients 35 satisfied study inclusion criteria. A total of 67 fluorescence in situ hybridization specimens were submitted. Upper tract transitional cell carcinoma was identified on 51 operative evaluations, of which 23 showed concurrent bladder tumor. For all encounters the sensitivity of fluorescence in situ hybridization was 56% and specificity was 80%. Sensitivity for low and high grade lesions was 68% and 67%, respectively. Only upper tract tumors were noted in 28 patients, in whom there were 2 false-positive and 13 false-negative voided fluorescence in situ hybridization results. In these cases sensitivity was 54% and specificity was 78% compared to the 18% sensitivity and 100% specificity of bladder cytology. Sensitivity for low and high grade upper tract transitional cell carcinoma was 60% and 50%, respectively. CONCLUSIONS: Voided fluorescence in situ hybridization has become an adjunct for bladder transitional cell carcinoma surveillance. However, it has limited value for upper tract tumor surveillance.	bladder
Lessons learned from 1,000 neobladders: the 90-day complication rate.	PURPOSE: We report the 90-day morbidity of the ileal neobladder in a large, contemporary, homogenous series of patients who underwent radical cystectomy at a tertiary academic referral center using a standard approach. MATERIALS AND METHODS: Between January 1986 and September 2008 we performed 1,540 radical cystectomies. A total of 281 patients had an absolute contraindication for orthotopic reconstruction. The remaining 1,259 patients were candidates for a neobladder. Of these patients 1,013 (66%) finally received a neobladder and form the basis of this report. All patients had a thorough followup until December 2008 or until death. All complications within 90 days of surgery were defined, categorized and classified by an established 5 grade and 11 domain modification of the original Clavien system. RESULTS: Of 1,013 patients 587 (58%) experienced at least 1 complication within 90 days of surgery. Infectious complications were most common (24%) followed by genitourinary (17%), gastrointestinal (15%) and wound related complications (9%). The 90-day mortality rate was 2.3%. Of the patients 36% had minor (grade 1 to 2) and 22% had major (grade 3 to 5) complications. On univariate analysis the incidence and severity of the 90-day complications rate correlate highly significantly with age, tumor stage, American Society of Anesthesiologists score and preoperative comorbidity. CONCLUSIONS: Radical cystectomy and ileal neobladder formation represent a major surgery with potential relevant early complications even in the most experienced hands. The rate of severe and lethal complications is acceptably low.	bladder
Exon 2 methylation inhibits hepaCAM expression in transitional cell carcinoma of the bladder.	AIM: We aimed to investigate the mechanisms of hepaCAM inactivation in transitional cell carcinoma of the bladder through the analysis of hepaCAM exon 2 methylation. METHODS: The methylation of hepaCAM exon 2 and the expression of hepaCAM were determined by methylation-specific restriction PCR assay and RT-PCR in bladder cancer cells (T24, BIU-87) as well as in 55 paired bladder cancer specimens. The methylated bladder cancer cells were treated with 5-Aza- 2'-deoxycytidine (5-Aza-CdR), a demethylating agent. MTT was used to detect the proliferation of T24 and BIU-87 cells. RESULTS: The proliferation of T24 and BIU-87 cells was suppressed by treatment with different concentrations of 5-Aza-CdR; the expression of hepaCAM was absent in T24 and BIU-87 cells, and we found that exon 2 of hepaCAM was methylated in the 2 cells. hepaCAM mRNA was re-expressed and the methylation status of hepaCAM exon 2 was reversed after treatment with 5-Aza-CdR. The expression of hepaCAM mRNA in bladder cancer tissues was significantly lower than that in adjacent tissues. The methylation rate of hepaCAM exon 2 was significantly higher in bladder cancer tissues than in adjacent tissues. The methylation of hepaCAM exon 2 was related to hepaCAM expression in bladder cancer tissues. CONCLUSIONS: Downregulation of hepaCAM expression plays an important role in the tumorigenesis and development of bladder cancer. DNA methylation may be important for downregulation of hepaCAM expression in bladder cancer.	bladder
Functional polymorphisms of cyclooxygenase-2 (COX-2) gene and risk for urinary bladder cancer in North India.	BACKGROUND: Cyclooxygenase-2 (COX-2) is an enzyme involved in the synthesis of prostaglandins and thromboxanes, which are regulators of processes that are relevant to cancer development. It is involved in carcinogenesis, immune response suppression, apoptosis inhibition, angiogenesis, and tumor cell invasion and metastasis. The gene for COX-2, designated as prostaglandin-endoperoxide synthase 2 (PTGS-2), carries polymorphisms, such as -765G>C, 1195G>A in the promoter region, and 8473T>C in the 3'-untranslated region (UTR), which have been associated with susceptibility to malignant disease. METHODS: We undertook a case-control study of 212 urothelial bladder cancer (UBC) cases and 250 controls to investigate the association between COX-2 polymorphism and bladder cancer susceptibility, using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method and also investigated gene-environment interactions. RESULTS: Cox-2 765G>C, a variant(C) allele carrier, was at an increased risk of UBC (odds ratio [OR] = 1.90; P = .004); however, -1195G>A; -1290A>G; and 3'UTR 8473T>C polymorphisms of COX-2 gene were not significantly associated with UBC. 765G>C also was associated with the invasive stage of a bladder tumor (OR = 2.73; P = .033). High risk for UBC also was observed with respect to COX-2 haplotypes C-765T8473A-1195A-1290 (OR = 3.47; P = .014). In case-only analysis, COX-2 765 variant allele carrier genotypes also showed an increased risk among former and current smokers (OR = 3.06; P = .041 and OR = 4.39; P = .032, respectively). CONCLUSION: COX-2 -765G>C polymorphism confers UBC susceptibility particularly in smokers and in patients with invasive tumors. 765C allele carrier genotypes also are influenced with a high risk of recurrence in Bacillus Calmette-Guérin-treated patients. Collectively, these findings confirm that the COX-2 -765G>C polymorphism is a risk factor for the development of bladder cancer and can provide a plausible mechanistic explanation. Further validation in large population-based studies is needed.	bladder
HAL blue-light cystoscopy in high-risk nonmuscle-invasive bladder cancer--re-TURBT recurrence rates in a prospective, randomized study.	OBJECTIVES: To evaluate the impact of hexaminolevulinate blue-light cystoscopy and transurethral resection of bladder tumors (TURBT) upon the short-term recurrence rate in high-risk nonmuscle-invasive bladder cancer (NMIBC) compared with conventional cystoscopy and resection. METHODS: Between December 2007 and November 2009, 446 patients were randomized for blue-light cystoscopy/resection and for standard cystoscopy/resection, respectively. The inclusion criteria consisted of positive urinary cytology and ultrasonographic suspicion of bladder tumors. High-risk NMIBC patients (carcinoma in situ [CIS], pTaG3, and pT1) from both series underwent standard Re-TURBT 6 weeks after the initial procedure. RESULTS: The proportions of CIS, pTaG3, and pT1 cases in the initial series were 13.1%, 5.7%, and 22.2% in the blue light series and 11.3%, 5.7%, and 23.3% in the white light series. In total, 72 and 64 high-risk cases, respectively, were diagnosed in the blue- and white-light series. The overall short-term recurrence rate at Re-TURBT was 11.1% for the blue-light group and 31.2% for the white-light group. The recurrence rates were 4.3% versus 27.8% for CIS, 10% versus 22.2% for pTaG3, and 15.4% versus 35.1% for pT1 cases, in favor of the blue-light arm. The recurrence rate in patients presenting with high-grade tumors was 17.2% in the blue-light group and 37% in the white-light group. CONCLUSIONS: Blue-light cystoscopy and resection significantly reduced the short-term recurrence rates determined during the standard Re-TURBT in all categories of high-risk patients compared with the standard cystoscopy and resection.	bladder
Gross hematuria in a 3-year-old girl caused by a large isolated bladder hemangioma.	Hemangiomas of the urinary tract can arise anywhere along the system. Although rare, these lesions can result in significant hematuria, with potential for patient morbidity. We report a case of an isolated bladder hemangioma identified in a 3-year-old girl presenting with recurrent high-volume gross hematuria. The lesion was not amenable to endoscopic resection because of its size. We present our operative management strategy as a potential method for other urologists who may be presented with similar scenarios.	bladder
Tumour node metastasis staging of bladder cancer: prognosis versus pitfalls.	PURPOSE OF REVIEW: The WHO classification of urothelial cancer in 2004 has made changes based on the insights of molecular genetics, indicating bladder cancer with entities that are genetically stable versus those that are genetically instable. Seen as work in progress, the need of further validation is obvious. Clinical studies based on solid histological diagnosis are as necessary as the definition of more molecular features of bladder cancer. RECENT FINDINGS: Solid histological diagnosis includes sufficient clinical information and adequate tissue processing. This combined with molecular data will lead to a more clear-cut distinction between benign and malignant and possibly to another change in terminology with higher concordance to other epithelial tumours. Whereas the identification of FGFR3 mutations has led to a better distinction of at least two pathways of urothelial carcinogenesis, additional multiparametric approaches may help improve the still inadequate search for urine and blood markers indicative of bladder cancer and/or its progression. Proteomic profiling, sets of epigenetic markers, and micro RNAs will be given as examples. SUMMARY: Recent data mainly support the concept of the WHO 2004 classification of bladder cancer. We are optimistic that an even more clear-cut distinction between benign recurring, nonprogressing tumours and more aggressive tumours will enable us to focus and limit chemotherapy.	bladder
Carcinomatous meningitis secondary to transitional cell bladder cancer.	We report a patient with carcinomatous meningitis secondary to known transitional cell carcinoma of the bladder. The patient presented with multiple focal neurological signs and symptoms. Diagnosis was suggested by magnetic resonance imaging and confirmed by analysis of the cerebrospinal fluid. He received whole brain radiotherapy despite a poor prognosis. To our knowledge, this is only the fifth reported case of neoplastic meningitis due to bladder cancer with confirmatory imaging and cytology and only the fourth reported case that presented with cranial nerve involvement.	bladder